Vanderbilt University School of Medicine

Mchaourab, Hassane S. , Ph.D.
Professor of Molecular Physiology and Biophysics
Professor of Chemistry
Louise B. McGavock Chair

Lab Url: http://www.mc.vanderbilt.edu/labs/mchaourab/

Phone Number: (615) 322-3307

Email Address:hassane.mchaourab@vanderbilt.edu

Mchaourab, Hassane's picture

Office Address   Mailing Address

741 Light Hall

741 Light Hall 0615


Research Keywords
Eye Lens Proteins, Heat Shock Proteins, neurotransmitter transporters, Multidrug transporters, structural biology, Spectroscopy,

Research Description
Research in the Mchaourab Laboratory is focused on understanding the structural and dynamic basis of protein function with focus on proteins that are involved in diseases. Using spectroscopic approaches, our laboratory studies the molecular aspect of: protein aggregation diseases such as cataract, the widespread phenomenon of multidrug resistance in cancer and infectious diseases and more recently neurotransmitter transport across the synaptic cleft in collaboration with Aurelio Galli?s Laboratory.

Lens aging, protein folding and Cataract: Small heat-shock proteins, including the major protein component in the lens alpha-crystallin, are molecular chaperones that help other proteins avoid aggregation. Protein aggregation is associated with many pathogenic conditions including alzheimer's diseases, mad cow disease and cataract. Our laboratory has pioneered novel assay to understand the mechanisms of both inherited and age-related cataract. We investigate small heat-shock proteins from various organisms and across the evolutionary spectrum.

Multidrug resistance in Cancer: Active drug extrusion by multidrug transporters is one of four general mechanisms associated with the multidrug resistance phenomenon, a key problem in the treatment of bacterial and fungal infections and cancers. The overexpression of adenosine triphosphate binding cassette (ABC) transporters is the most frequent cause of resistance to cytotoxic agents. In addition, mutations in the genes encoding the 48 human ABC transporters are associated with diseases such as cystic fibrosis, Tangier disease and adrenoleukodystrophy. Our laboratory is investigating how these transporters work, a key step in the design of therapeutic strategies.

Neurotransmitter transport: Chemical synapses are junctions at which electrical signals are relayed from one neuron to another via release of neurotransmitters such as dopamine, serotonin and norepinephrine. The process of clearing these molecules controls the magnitude and duration of synaptic signaling. Neurotransmitter transporters are integral membrane proteins that move neurotransmitter back into the neuronal terminal thus terminating signaling. In collaboration with the Galli laboratory at Vanderbilt, we are investigating the process of transport as well as its modulation by kinases. A future goal is to determine the structural basis of antidepressants, amphetamine and cocaine effects on the properties of these transporters.

Publications
Amadi, ST, Koteiche, HA, Mishra, S, McHaourab, HS. Structure, dynamics, and substrate-induced conformational changes of the multidrug transporter EmrE in liposomes. J Biol Chem, 285(34), 26710-8, 2010.

Claxton, DP, Quick, M, Shi, L, de Carvalho, FD, Weinstein, H, Javitch, JA, McHaourab, HS. Ion/substrate-dependent conformational dynamics of a bacterial homolog of neurotransmitter:sodium symporters. Nat Struct Mol Biol, 17(7), 822-9, 2010.

Zou, P, McHaourab, HS. Increased sensitivity and extended range of distance measurements in spin-labeled membrane proteins: Q-band double electron-electron resonance and nanoscale bilayers. Biophys J, 98(6), L18-20, 2010.

Kumar, MS, Koteiche, HA, Claxton, DP, Mchaourab, HS. Disulfide cross-links in the interaction of a cataract-linked alphaA-crystallin mutant with betaB1-crystallin. FEBS Lett, 583(1), 175-9, 2009. PMCID:2787765

Latham, JC, Stein, RA, Bornhop, DJ, Mchaourab, HS. Free-solution label-free detection of alpha-crystallin chaperone interactions by back-scattering interferometry. Anal Chem, 81(5), 1865-71, 2009. PMCID:2787765

McHaourab, HS, Godar, JA, Stewart, PL. Structure and mechanism of protein stability sensors: chaperone activity of small heat shock proteins. Biochemistry, 48(18), 3828-37, 2009. PMCID:2785012

Smriti, , Zou, P, McHaourab, HS. Mapping daunorubicin-binding Sites in the ATP-binding cassette transporter MsbA using site-specific quenching by spin labels. J Biol Chem, 284(20), 13904-13, 2009. PMCID:2679490

Zou, P, Bortolus, M, McHaourab, HS. Conformational cycle of the ABC transporter MsbA in liposomes: detailed analysis using double electron-electron resonance spectroscopy. J Mol Biol, 393(3), 586-97, 2009.

Zou, P, McHaourab, HS. Alternating access of the putative substrate-binding chamber in the ABC transporter MsbA. J Mol Biol, 393(3), 574-85, 2009.

Claxton, DP, Zou, P, Mchaourab, HS. Structure and orientation of T4 lysozyme bound to the small heat shock protein alpha-crystallin. J Mol Biol, 375(4), 1026-39, 2008. PMCID:2276617

McHaourab, HS, Mishra, S, Koteiche, HA, Amadi, SH. Role of sequence bias in the topology of the multidrug transporter EmrE. Biochemistry, 47(31), 7980-2, 2008.

Borbat, PP, Surendhran, K, Bortolus, M, Zou, P, Freed, JH, McHaourab, HS. Conformational Motion of the ABC Transporter MsbA Induced by ATP Hydrolysis. PLoS Biol, 5(10), e271, 2007. PMCID:2001213

Koteiche, HA, Kumar, MS, McHaourab, HS. Analysis of betaB1-crystallin unfolding equilibrium by spin and fluorescence labeling: evidence of a dimeric intermediate. FEBS Lett, 581(10), 1933-8, 2007. PMCID:2394508

McHaourab, HS, Kumar, MS, Koteiche, HA. Specificity of alphaA-crystallin binding to destabilized mutants of betaB1-crystallin. FEBS Lett, 581(10), 1939-43, 2007. PMCID:2219212

Mori, T, Williams, DR, Byrne, MO, Qin, X, Egli, M, Mchaourab, HS, Stewart, PL, Johnson, CH. Elucidating the ticking of an in vitro circadian clockwork. PLoS Biol, 5(4), e93, 2007. PMCID:1831719

Zou, P, Surendhran, K, Mchaourab, HS. Distance measurements by fluorescence energy homotransfer: evaluation in T4 lysozyme and correlation with dipolar coupling between spin labels. Biophys J, 92(4), L27-9, 2007. PMCID:1783887

Koteiche, HA, Mchaourab, HS. Mechanism of a hereditary cataract phenotype. Mutations in alphaA-crystallin activate substrate binding. J Biol Chem, 281(20), 14273-9, 2006.

Shi, J, Koteiche, HA, McHaourab, HS, Stewart, PL. Cryoelectron microscopy and EPR analysis of engineered symmetric and polydisperse Hsp16.5 assemblies reveals determinants of polydispersity and substrate binding. J Biol Chem, 281(52), 40420-8, 2006.

Altenbach, C, Froncisz, W, Hemker, R, McHaourab, H, Hubbell, WL. Accessibility of nitroxide side chains: absolute Heisenberg exchange rates from power saturation EPR. Biophys J, 89(3), 2103-12, 2005. PMCID:1366712

Dong, J, Yang, G, McHaourab, HS. Structural basis of energy transduction in the transport cycle of MsbA. Science, 308(5724), 1023-8, 2005.

Koteiche, HA, Chiu, S, Majdoch, RL, Stewart, PL, McHaourab, HS. Atomic Models by Cryo-EM and Site-Directed Spin Labeling: Application to the N-Terminal Region of Hsp16.5. Structure (Camb), 13(8), 1165-71, 2005.

Shashidharamurthy, R, Koteiche, HA, Dong, J, McHaourab, HS. Mechanism of chaperone function in small heat shock proteins: dissociation of the HSP27 oligomer is required for recognition and binding of destabilized T4 lysozyme. J Biol Chem, 280(7), 5281-9, 2005.

Sathish, Hasige S., Koteiche, Hanane A., McHaourab, Hassane S.. Destabilized mutants of {beta}B2-crystallin. Insight into the folding equilibrium and the determinants of binding to a-crystallin. J Biol Chem, , , 2004.

Koteiche, Hanane A, McHaourab, Hassane S. Mechanism of chaperone function in small heat-shock proteins. Phosphorylation-induced activation of two-mode binding in alphaB-crystallin. J Biol Chem, 278(12), 10361-7, 2003.

Koteiche, Hanane A, Reeves, Matthew D, McHaourab, Hassane S. Structure of the substrate binding pocket of the multidrug transporter EmrE: site-directed spin labeling of transmembrane segment 1. Biochemistry, 42(20), 6099-105, 2003.

Sathish, Hasige A, Stein, Richard A, Yang, Guangyong, Mchaourab, Hassane S. Mechanism of chaperone function in small heat-shock proteins. Fluorescence studies of the conformations of T4 lysozyme bound to alphaB-crystallin. J Biol Chem, 278(45), 44214-21, 2003.

Borbat, Petr P, McHaourab, Hassane S, Freed, Jack H. Protein structure determination using long-distance constraints from double-quantum coherence ESR: study of T4 lysozyme. J Am Chem Soc, 124(19), 5304-14, 2002.

Koteiche, Hanane A, Mchaourab, Hassane S. The determinants of the oligomeric structure in Hsp16.5 are encoded in the alpha-crystallin domain. FEBS Lett, 519(1-3), 16-22, 2002.

Mansoor, Steven E, McHaourab, Hassane S, Farrens, David L. Mapping proximity within proteins using fluorescence spectroscopy. A study of T4 lysozyme showing that tryptophan residues quench bimane fluorescence. Biochemistry, 41(8), 2475-84, 2002.

Mchaourab, Hassane S, Dodson, Erich K, Koteiche, Hanane A. Mechanism of chaperone function in small heat shock proteins. Two-mode binding of the excited states of T4 lysozyme mutants by alphaA-crystallin. J Biol Chem, 277(43), 40557-66, 2002.

Bova MP, Mchaourab HS, Han Y, and Fung BK. Subunit exchange of small heat-shock proteins. Analysis of oligomer formation of A-crystallin and Hsp27 by Fluorescence energy transfer and site-directed truncations. J. Biol. Chem, 275, 1035-42, 2000.

Bova, M P, McHaourab, H S, Han, Y, Fung, B K. Subunit exchange of small heat shock proteins. Analysis of oligomer formation of alphaA-crystallin and Hsp27 by fluorescence resonance energy transfer and site-directed truncations. J Biol Chem, 275(2), 1035-42, 2000.

Haley DA, Bova MP, Huang QL, Mchaourab HS, and Stewart PL. Small heat-shock protein structures reveal a continuum from symmetric to variable assemblies. J. Mol. Biol., 298, 261-272, 2000.

Haley, D A, Bova, M P, Huang, Q L, Mchaourab, H S, Stewart, P L. Small heat-shock protein structures reveal a continuum from symmetric to variable assemblies. J Mol Biol, 298(2), 261-72, 2000.

Kaplan RS, Mayor JA, Kotaria R, Walters DE, and Mchaourab HS. The yeast mitochondrial citrate transport protein: determination of secondary structure and solvent accessibility of transmembrane domain IV using site-directed spin labeling. Biochemistry, 39, 9157-63, 2000.

Kaplan, R S, Mayor, J A, Kotaria, R, Walters, D E, McHaourab, H S. The yeast mitochondrial citrate transport protein: determination of secondary structure and solvent accessibility of transmembrane domain IV using site-directed spin labeling. Biochemistry, 39(31), 9157-63, 2000.

Barnes JP, Liang Z, Mchaourab HS, Freed JH, and Hubbell WL. A multifrequency electron spin resonance study of T4 lysozyme dynamics. Biophys. J, 76, 3298-3306 , 1999.

Barnes, J P, Liang, Z, Mchaourab, H S, Freed, J H, Hubbell, W L. A multifrequency electron spin resonance study of T4 lysozyme dynamics. Biophys J, 76(6), 3298-306, 1999. PMCID:1300299

Berengian AR, Parfenova M, and Mchaourab HS. Site- directed spin labeling study of subunit interactions in the alpha-crystallin domain of small heat-shock proteins. Comparison of the oligomer symmetry in alphaA-crystallin, HSP27, and HSP16.3. J. Biol. Chem, 274, 6305-6314, 1999.

Berengian, A R, Parfenova, M, Mchaourab, H S. Site-directed spin labeling study of subunit interactions in the alpha-crystallin domain of small heat-shock proteins. Comparison of the oligomer symmetry in alphaA-crystallin, HSP 27, and HSP 16.3. J Biol Chem, 274(10), 6305-14, 1999.

Koteiche HA and Mchaourab HS. Folding pattern of the alpha-crystallin domain determined by site-directed spin labeling. J. Mol. Biol. , 294, 561-577 , 1999.

Koteiche, H A, Mchaourab, H S. Folding pattern of the alpha-crystallin domain in alphaA-crystallin determined by site-directed spin labeling. J Mol Biol, 294(2), 561-77, 1999.

Mansoor SE, Mchaourab HS, ans Farrens DL. Determination of protein secondary structure and solvent accessibility using site-directed fluorescence labeling. Studies of T4 lysozyme using the fluorescent probe monobromobimane. Biochemistry, 38, 16383-16393 , 1999.

Mansoor, S E, McHaourab, H S, Farrens, D L. Determination of protein secondary structure and solvent accessibility using site-directed fluorescence labeling. Studies of T4 lysozyme using the fluorescent probe monobromobimane. Biochemistry, 38(49), 16383-93, 1999.

Mchaourab HS, Kalai T, Hideg K, and Hubbell WL. Motion of spin labeled side chains in T4 lysozyme: effect of side chain structure. Biochemistry , 38, 2947 55 , 1999.

Mchaourab, H S, K?!lai, T, Hideg, K, Hubbell, W L. Motion of spin-labeled side chains in T4 lysozyme: effect of side chain structure. Biochemistry, 38(10), 2947-55, 1999.

Hyde JS, Mchaourab HS, Camenisch T, Ratke JJ, Cox RW, and Froncisz W. EPR detection by time-locked sub-sampling. Rev. Sci. Instrum, 69, 2622-2628 , 1998.

Koteiche HA, Berengian AR, and Mchaourab HS. Identification of protein folding patterns using site-directed spin labeling. Structural characterization of a -sheet and putative substrate binding regions in the conserved domain of A-crystallin. Biochemistry , 37, 126821-12688 , 1998.

Koteiche, H A, Berengian, A R, Mchaourab, H S. Identification of protein folding patterns using site-directed spin labeling. Structural characterization of a beta-sheet and putative substrate binding regions in the conserved domain of alpha A-crystallin. Biochemistry, 37(37), 12681-8, 1998.

Berengian AR, Bova MP, and Mchaourab HS. Structure and function of the conserved domain in A-crystallin. Site-directed spin labeling identifies a -strand located near a subunit interface. Biochemistry , 36, 9951-9957 , 1997.

Berengian, A R, Bova, M P, Mchaourab, H S. Structure and function of the conserved domain in alphaA-crystallin. Site-directed spin labeling identifies a beta-strand located near a subunit interface. Biochemistry, 36(33), 9951-7, 1997.

Mchaourab HS, Berengian A, and Koteiche HA. Site-directed spin-labeling study of the structure and subunit interactions along a conserved sequence in the -crystallin domain of heat-shock protein 27. Evidence of a conserved subunit interface. Biochemistry , 36, 14627-14634 , 1997.

Mchaourab HS, Oh KJ, Fang CJ, and Hubbell WL. The conformation of T4 lysozyme in solution. Hinge bending motion and the substrate-induced conformational transition studied by site-directed spin labeling. Biochemistry , 36, 307-316 , 1997.

Mchaourab, H S, Berengian, A R, Koteiche, H A. Site-directed spin-labeling study of the structure and subunit interactions along a conserved sequence in the alpha-crystallin domain of heat-shock protein 27. Evidence of a conserved subunit interface. Biochemistry, 36(48), 14627-34, 1997.

Mchaourab, H S, Oh, K J, Fang, C J, Hubbell, W L. Conformation of T4 lysozyme in solution. Hinge-bending motion and the substrate-induced conformational transition studied by site-directed spin labeling. Biochemistry, 36(2), 307-16, 1997.

Hubbell WL, Mchaourab HS, Altenbach C, and Lietzow M. Watching proteins move using site-directed spin labeling. Structure , 4, 779-783 , 1996.

Hubbell, W L, Mchaourab, H S, Altenbach, C, Lietzow, M A. Watching proteins move using site-directed spin labeling. Structure, 4(7), 779-83, 1996.

Mchaourab HS, Lietzow MA, Hideg K, and Hubbell WL. Motion of spin-labeled side chains in T4 lysozyme. Correlation with protein structure and dynamics. Biochemistry , 35, 7692-7704 , 1996.

Mchaourab, H S, Lietzow, M A, Hideg, K, Hubbell, W L. Motion of spin-labeled side chains in T4 lysozyme. Correlation with protein structure and dynamics. Biochemistry, 35(24), 7692-704, 1996.

Hyde JS, Strangeway RA, Luglio J, Mchaourab HS, and Froncisz W. Noise in EPR bridges with multiple time-locked microwave frequencies. Bull. Magn. Reson, 17, 54-60, 1995.

Singh RJ, Feix JB, Mchaourab HS, Hogg N, and Kalyanaraman B. Spin labeling study of the oxidative damage to low-density lipoprotein. Arch. Biochem. Biophys, 320, 155 , 1995.

Singh RJ, Hogg N, Mchaourab HS, and Kalyanaraman B. Physical and chemical interactions between nitric oxide and nitroxides. Biochim. Biophys. Acta , 1201, 437 , 1995.

Singh, R J, Feix, J B, Mchaourab, H S, Hogg, N, Kalyanaraman, B. Spin-labeling study of the oxidative damage to low-density lipoprotein. Arch Biochem Biophys, 320(1), 155-61, 1995.

Strangeway RA, Mchaourab HS, Luglio JR, Froncisz W, and Hyde JS. A general multipurpose multiquantum EPR spectrometer. Rev. Sci. Instrum, 66, 4516-4528 , 1995.

Mchaourab HS, Hyde JS, and Feix JB. Binding and state of aggregation of spin-labeled cecropin AD in phospholipid bilayers: effect of surface charge and fatty acyl chain length. Biochemistry, 33, 6691, 1994.

Mchaourab HS, Hyde JS, and Feix JB. Aggregation state of spin-labeled cecropin AD in solution. Biochemistry, 33, 11895, 1994.

Mchaourab, H S, Hyde, J S, Feix, J B. Binding and state of aggregation of spin-labeled cecropin AD in phospholipid bilayers: effects of surface charge and fatty acyl chain length. Biochemistry, 33(21), 6691-9, 1994.

Singh, R J, Hogg, N, Mchaourab, H S, Kalyanaraman, B. Physical and chemical interactions between nitric oxide and nitroxides. Biochim Biophys Acta, 1201(3), 437-41, 1994.

Mchaourab HS and Hyde JS. Dependence of the multiquantum EPR signal on the spin-lattice relaxation time. Effect of oxygen in spin-labeled membranes. J. Magn. Reson, 101B, 1748 , 1993.

Mchaourab HS and Hyde JS. Continuous wave multiquantum EPR spectroscopy. III. Theory of intermodulation sidebands. J. Chem. Phys, 98, 1786 , 1993.

Mchaourab HS, Christidis TC, and Hyde JS. Continuous wave multiquantum EPR spectroscopy. IV. Multiquantum electron-nuclear double resonance. J. Chem. Phys, 99, 4975, 1993.

Mchaourab HS, Pfenninger S, Antholine WE, Felix CC, Hyde JS, and Kroneck PMH. Multiquantum EPR of the copper mixed valence site in nitrous oxide reductase. Biophys. J. , 64, 1576 , 1993.

Mchaourab, H S, Hyde, J S, Feix, J B. Aggregation state of spin-labeled cecropin AD in solution. Biochemistry, 32(44), 11895-902, 1993.

Mchaourab, H S, Pfenninger, S, Antholine, W E, Felix, C C, Hyde, J S, Kroneck, P M. Multiquantum EPR of the mixed valence copper site in nitrous oxide reductase. Biophys J, 64(5), 1576-9, 1993. PMCID:1262484

Mchaourab HS, Christidis TC, Froncisz W, Sczaniecki PB, and Hyde JS. Multiple quantum electron-electron double resonance. J. Magn. Reson, 92, 420 , 1991.


Postdoctoral Position Available
Yes

Postdoctoral Position Details
Postdoctoral position available in an interdisciplinary research program to investigate conformational changes during the functional cycles of multidrug transporters and/or the functional mechanism of small heat-shock proteins including lens a-crystallins. The experimental approach relies heavily on site-directed spin and fluorescence labeling and associated electron paramagnetic resonance and fluorescence spectroscopies. We are looking for a recent Ph.D. who is comfortable with these approaches and interested in learning new biophysical and biochemical techniques. Applicants should send a CV and 3 letters of recommendations to:
Hassane Mchaourab, Ph.D.
Department of Molecular Physiology and Biophysics
Vanderbilt University Medical Center
2215 Garland Avenue / 741 Light Hall
Nashville Tennessee 37232
Email:hassane.mchaourab@vanderbilt.edu


Updated Date
08/20/2008



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